Implantable reservoir and system for delivery of a therapeutic agent

ABSTRACT

There is disclosed method and apparatus for retaining a reservoir for a therapeutic agent between the scalp and cranium of a subject, including providing a deformable pouch or rigid cylinder for dispensing the therapeutic agent from the reservoir to a location in the body of the subject. In one embodiment, a pump is used to pump the agent from the reservoir to the location in the subject&#39;s body. In another example embodiment, there is provided method and apparatus for forming at least one cavity in the cranium of the subject, and placing at least a portion of the pump in the cavity. Power is applied to the pump in a variety of ways.

RELATED APPLICATIONS

[0001] This application is a continuation application of U.S. patentapplication Ser. No. 09/790,982, filed Feb. 22, 2001, which applicationis incorporated herein by reference.

TECHNICAL FIELD OF THE INVENTION

[0002] This invention relates generally to the field of medicine, andmore particularly to implantable devices for delivering therapeuticagents to a body.

BACKGROUND OF THE INVENTION

[0003] Localized drug therapy has been shown to be successful forchronic pain treatment and chemotherapy for spinal disorders using lessdrugs and without the potential adverse effects of a systemic dosage.Pumps for abdominal implant have been designed to dispense drugs aseither continual dosage through a constant pressure, non-electricalmeans or as programmable, periodic dispensing through the use of anelectrically driven pump and constant pressure reservoir.

[0004] More recently, the value of localized drug therapy forneurological disorders has been identified. Existing pumps, whilepotentially providing the therapeutic advantages of implantable infusionpumps, are large and are implanted abdominally. Such pumps if used willrequire a catheter tunneled from the abdominal implant site, through theneck to an entry site in the head, and then to the localized treatmentsite.

[0005] Present electrically powered pumps use primary (non-rechargeable)batteries as their power source. When the battery is depleted in thesedevices, the complete assembly must be removed and replaced.Rechargeable batteries have been used in previous implant devicesincluding earlier pacemakers and present day artificial hearts and leftventricular assist devices (LVAD's). Artificial hearts and LVAD'srequire the use of an external power source due to the high power demandof the pumping system that would deplete an internal battery quickly.They also use a rechargeable battery to provide power for a patient whenexternal power is not appropriate, such as when taking a shower or bath.Earlier pacemakers used a nickel cadmium rechargeable battery systemthat relied on the patient to recharge transcutaneously on a periodicbasis.

SUMMARY OF THE INVENTION

[0006] According to one aspect, the present invention provides methodand apparatus for retaining a reservoir for a therapeutic agent betweenthe scalp and cranium of a subject. According to another aspect, thereis provided method and apparatus for dispensing the therapeutic agentfrom the reservoir to a location in the body of the subject. Accordingto yet another aspect, there is provided method and apparatus forpumping the agent to the location in the subject's body with a pump.According to still another aspect, there is provided method andapparatus for forming at least one cavity in the cranium of the subject,and placing at least a portion of the pump in the cavity. According tostill other aspects of the method and apparatus, power is supplied tothe pump. These and other aspects of the invention are described below.

BRIEF DESCRIPTION OF THE DRAWINGS

[0007]FIGS. 1A and 1B show therapeutic agent reservoirs according tocertain example embodiments of the invention;

[0008]FIG. 2 shows a multiple reservoir system according to oneembodiment of the invention;

[0009]FIGS. 3A and 3B show a side view of a reservoir housing accordingto one example embodiment of the invention;

[0010]FIG. 4 shows a reservoir implanted in the back according to oneembodiment of the invention;

[0011]FIG. 5 shows a reservoir deployment system according to oneembodiment of the invention;

[0012]FIG. 6 shows a reservoir refill system according to one embodimentof the invention;

[0013]FIGS. 7 and 8 show a reservoir refill systems according to exampleembodiments of the invention;

[0014]FIG. 9 shows a multiple reservoir system with multiple therapeuticagents stored therein according to one embodiment of the invention;

[0015]FIGS. 10-15 show various reservoir systems according to variousembodiments of the invention;

[0016]FIG. 16 shows an implanted system according to one embodiment ofthe invention;

[0017]FIG. 17 shows an implanted unit having a telemetry control systemaccording to one embodiment of the invention;

[0018]FIG. 18 shows a closed loop feedback system according to oneembodiment of the invention;

[0019]FIG. 19 shows an implanted unit according to one embodiment of theinvention;

[0020]FIG. 20 shows two example deployments according to one embodimentof the invention;

[0021]FIGS. 21-23 show power system configurations according to oneembodiment of the invention;

[0022]FIG. 24 shows an example implant unit according to one embodimentof the invention;

[0023]FIG. 25 shows a perspective view of an implanted multiplereservoir system according to one embodiment of the invention;

[0024]FIG. 26 shows a telemetry/control system according to oneembodiment of the invention.

DETAILED DESCRIPTION

[0025] In the following detailed description of sample embodiments ofthe invention, reference is made to the accompanying drawings which forma part hereof, and in which is shown by way of illustration specificsample embodiments in which the invention may be practiced. Theseembodiments are described in sufficient detail to enable those skilledin the art to practice the invention, and it is to be understood thatother embodiments may be utilized and that logical, mechanical,electrical and other changes may be made without departing from thespirit or scope of the present invention. The following detaileddescription is, therefore, not to be taken in a limiting sense, and thescope of the present invention is defined only by the appended claims.

EXAMPLE METHODS

[0026] There is described below a number of example embodiments of theinvention relating to dispensing a therapeutic agent from an implantedreservoir to a treatment site in a subject's body. According to a firstexample embodiment of the methods of the invention, a reservoir for atherapeutic agent is retained between the scalp and cranium of asubject. In another embodiment, the reservoir is positioned proximate asubject's spinal. In another embodiment, the reservoir is hermeticallysealed, for example with a metallic substance, such as a metal foil orhard casing.

[0027] In yet another embodiment, the agent is stored in a reservoirhaving one or more bladders or pouches adapted to occupy a substantiallyplanar space. Yet still another example embodiment of the methods of theinvention provides that the reservoir is deployed in the space betweenthe scalp and cranium using one or more deployment lines connected at ornear the edge of the reservoir that when pulled deploy the reservoir ina desired position.

[0028] In yet another example embodiment, where there is more than onebladder, and the bladders are connected with at least one fluid conduitallowing therapeutic agent to flow from one bladder to the other.

[0029] According to another embodiment of the methods of the invention,the reservoir is refilled using a hypodermic needle that is insertedtranscutaneously and into a refill port on the reservoir or connected tothe reservoir that is adapted to receive the needle.

[0030] In yet another example embodiment, the reservoir is substantiallyplanar, and the port is oriented so that the needle is inserted along aline that is generally parallel to the plane of the reservoir. Where, inone example embodiment, the reservoir is substantially planar, the portis oriented so that the needle is inserted along a line that isgenerally perpendicular to the plane of the reservoir. In anotherembodiment, the port is connected to the reservoir through a fluidconduit, and the port position spaced apart from the reservoir, forexample behind the ear, with the conduit tunneled under the scalp.

[0031] In another example embodiment, the reservoir is substantiallyplanar, and the edges of the housing of the reservoir taper from asmaller thickness at the edge to a greater thickness away from the edge.

[0032] Still another example embodiment of the methods of the inventionprovides for holding one or more different therapeutic agents in one ormore additional implanted reservoirs, and dispensing the differentagents from each reservoir.

[0033] In one more example embodiment of the methods of the invention,the reservoir is retained subcutaneously between the subject's galeaaponeurotica and cranium so that the reservoir outline is imperceptibleto a casual observer. In this case or others the reservoir is anchoredby suturing to the subject's galea or other tissue.

[0034] Where the reservoir is a pouch, one embodiment by exampleprovides that the pouch is held dimensionally fixed on all axes exceptone. In another example embodiment, the pouch is formed at least in partwith a silicone or polymer.

[0035] In a further embodiment, wherein the reservoir is a pouch, andwhen the reservoir is full, the pouch is confined by a solid surfacesuch as the inside of an outer hermetic enclosure or a molded plasticrestrainer.

[0036] In a still further embodiment, one end of the reservoir has afixed dimension and contains an outlet port and a filling port, with theopposing end having a non-fixed dimension and is activated by a push rodor piston mechanism to predictably collapse the pouch while pushing thetherapeutic agent out under constant pressure.

[0037] In yet still another embodiment, a screw or impeller pump islocated at the fixed end of the reservoir and withdraws the agent fromthe reservoir. In one such example embodiment, the reservoir is a pouchand the agent is pumped from the pouch, and the pouch collapses as it isemptied, maintaining the appropriate pressure/volume ratio inside thehermetic enclosure and thereby eliminating a vacuum within thereservoir. Another example embodiment provides that the reservoir is asolid cylinder with the outlet port or valve mechanism located on oneend of the cylinder, and the opposing end is fitted with a pushrod/sealing piston to retain the therapeutic agent and to force theagent through the outlet port. Another embodiment provides that after aninfusion cycle, the drive or stepper motor reverses enough to releasepressure on the therapeutic agent chamber and to maintain a slightnegative pressure in relation to that of the surrounding anatomy.

[0038] In one example embodiment of the methods, the reservoir is asquare or round hollow, rigid tube coiled to maintain a flat orspecifically shaped profile of minimum surface area, and the reservoiris filled through an inflow valve located at or near one end of thetube, and the outflow port is located at the opposite end of the tubefrom the filling port.

[0039] According to another example embodiment the reservoir is formedfrom a collection of multiple reservoirs, connected by tubing, designedto provide a flexible or contoured implant device shape that can form tothe shape of the subject's cranium, and wherein the reservoir is filledby syringe through a fill port attached to one of the reservoir sectionsand thereby fills all reservoir sections through the connected tubing.In another embodiment, the reservoir(s) is contoured to the shape of asubject's lower back.

[0040] In still another embodiment, a pump that will pump agent from thereservoir is located in a manner that provides complete drainage of allreservoirs sections during a therapy cycle.

[0041] According to yet another example embodiment of the methods thereservoir is refilled through a sealed silicone portal that is accessedby a needle through the skin.

[0042] According to still another embodiment, the therapeutic agent isdispensed from a reservoir under the scalp to a location in the brain ofthe subject. In another embodiment, the therapeutic agent is dispensedfrom a reservoir located in the soft tissue of the lower back to alocation in the spine of the subject. Such dispensing is done in oneexample embodiment based on programmed parameters. Such programmedparameters are for example telemetered transcutaneously. Further,information may be telemetered transcutaneously from a pumping device toa device outside the subject's body.

[0043] In yet another embodiment still, agent is dispensed using a fluidconduit with a proximal end coupled to receive agent from the reservoirand a distal end positioned in the brain of the subject.

[0044] The therapeutic agent is thus, in this example, dispensed bypumping it to the location in the subject's body with a pump, that is inone example embodiment selected from the group of: a screw, impeller,diaphragm, or piston type pump. In yet still another example embodiment,the pump is a screw or impeller type motor driven by a stepper ormicrostepper motor that is accurately controlled to regulate the dosagevolume by number of rotations of the screw or impeller. Still anotherembodiment provides that the pump is a diaphragm pump or piston pumpthat controls dosage volume by change in volume per stroke multiplied bythe number of strokes. In one embodiment, the pump is a micromachinedevice or an ultrasonic piezoelectric device. For example, a pump suchas described in “A High-Performance Silicon Micropump for an ImplantableDrug Delivery System”, D. Maillefer, et al. MEMS '99 conference. Or, apump such as that described in “Piezoelectric Flexural-Traveling-WavePumps”. JPL New Technology Report NPO-19737. National Aeronautics andSpace Administration.

[0045] In still other embodiments, the outflow of agent from thereservoir is controlled using a first valve to regulate the inflow and asecond valve to regulate the outflow.

[0046] Yet another embodiment provides that the inflow valve is amechanical valve displaced by the refill needle. In one exampleembodiment, the inflow valve is an electronically controlled valve thatis activated by an external device at the time of filling, and/or theoutflow valve is electronically controlled and timed to the outflowcycle of the pump. In this arrangement, for instance, the outflow valveis a normally closed valve located at the distal end of a cathetercarrying the therapeutic agent to the location in the subject's body,and when therapeutic agent delivery is required, the valve iselectrically opened and remains open for a programmed period of time.

[0047] According to yet one more embodiment, the conductors for thevalve are embedded in the sidewall of the catheter.

[0048] In still another embodiment, the output valve is located at adischarge port of the pump device, and opened electrically.

[0049] In still another arrangement, there is provided a closed loopsensory mechanism that determines when to deliver a dosage oftherapeutic agent and how much therapeutic agent dosage is appropriate.

[0050] Yet another example embodiment provides for forming at least onecavity in the cranium of the subject, and placing at least a portion ofthe pump in the cavity.

[0051] Yet more example embodiments provide for positioning the pump orelectronics inside the body of the subject at a location other than thetop of the head of the subject, or under the skin behind the ear of thesubject, or in the chest region of the subject.

[0052] In still more embodiments, power is transmitted to the pumptranscutaneously, or an implanted power source is retained within thesubject's body, wherein the power source powers the pump, and forexample the power source is rechargeable. Such rechargeable power sourceis a rechargeable battery or storage capacitor. The rechargeable powersource is recharged in this embodiment, for example, by transcutaneouslytransmitting power to the power source.

[0053] Still other embodiments provide that the power source is integralwith electronic circuitry used to control the pump.

[0054] In some operational modes for example, the therapeutic agent ispumped when an external power source is placed over the site of thepump.

[0055] The methods of the invention further provide in one examplearrangement for forming at least one cavity in the cranium of thesubject, and placing at least a portion of the power source in thecavity.

[0056] In some example configurations, the power source is positionedinside the body of the subject at a location other than the location ofthe pouch and/or pump, for example positioning the power source underthe skin behind the ear of the subject, or in the chest region of thesubject.

[0057] In still more example embodiments, one or more electroniccomponents are adapted to control the dispensing of therapeutic agentfrom the reservoir to the subject's body. Such electronic components insome example configurations are contained in a hermetically sealedcontainer suitable for long term human implant. Such a container is, forexample, constructed of one or more materials from the following group:titanium and stainless steel.

[0058] Further, in yet still more example embodiments, the components orthe pump are enclosed in a fluid-tight enclosure and all components andconnections are hermetically sealed against potential moisture relatedfailures.

[0059] In addition, in another example configuration, at least onecavity is formed in the cranium of the subject and at least portions ofthe components are kept in the cavity.

[0060] In yet more example embodiments of the methods, more than onecavities or burrholes are formed in a subject's cranium, and at least aportion of a pump is retained in one cavity and at least a portion of apower source for the pump in the other cavity.

[0061] Yet another example embodiment provides that electronic circuitryoperates the pump based on programmed parameters.

[0062] An external device is provided on one example embodiment totelemeter signals into and out of the electronic circuitry. In such anexample embodiment, the external device reprograms the electroniccircuitry as necessary, and collects and displays data as transmittedfrom the implantable device. Further, the external electronic device insome embodiments signals the electronic circuitry to cause an extra doseof therapeutic agent to be delivered upon demand by an operator. In someexample configurations, the bidirectional transmitting provides signalsto activate the circuitry within the implant device and relay statusinformation from the circuitry to outside the subject's body. Suchsignals include in some example cases starting energy and signaltransmission either automatically by proximity of the external device tothe implanted device or by a control activated by an operator.

[0063] To provide for hermetic operation, in some example embodimentsthe electronic circuitry is enclosed in a fluid-tight enclosure and allelectrical components and connections are hermetically sealed againstpotential moisture related failures.

[0064] In still yet another example embodiment, therapeutic agent ispumped using a pump and power source, and further wherein the pump andpower source are housed integral to the pump and reservoir. In yetanother configuration, there is included a pump and power source, andfurther the power source is located remotely from the reservoir. Suchpump or power source are, in some example cases, implanted in thesubject's body.

[0065] According to one more example embodiment, single or multipleconductors carry power from the power source to the pump, and theconductors are encased in a biocompatible flexible material, and thebiocompatible material is selected from the group of: silicone orpolyurethane.

[0066] In still one more example embodiment, the conductors arepermanently attached to the pump and electronic components forcontrolling the pump in a manner that allows them to be disconnected. Inone such embodiment, the wires are attached permanently to the pump. Inanother embodiment, they are attached permanently to the electronicpower source.

[0067] Thus there has been described above various example methods forstoring and dispensing a therapeutic agent from a subject's body. Thesemethods are not limited to any particular apparatus. However, exampleapparatus are illustrated below.

EXAMPLE APPARATUS

[0068] The present invention provides a number of example apparatusrelating to dispensing a therapeutic agent from an implanted reservoirto a treatment site in a subject's body. According to a first exampleembodiment of the apparatus shown in FIG. 1A, there is provided areservoir 10 for a therapeutic agent. In one example embodiment, thereservoir 10 is adapted to be implanted between the scalp 12 and cranium14 of a subject. In another embodiment shown in FIG. 1B, the reservoir10 is adapted to be implanted under the skin 15 in the soft tissue 13 ofthe back near the spine. In one embodiment, a housing for the reservoiris adapted or contoured to conform to the anatomical features of theback in the area in which the implant of the housing is sought to bemade.

[0069] In yet another embodiment shown in FIG. 2, the agent is stored ina reservoir 20 having one or more bladders or pouches 22 adapted tooccupy a substantially planar space between the scalp 12 and cranium 14.According to one example embodiment shown above in FIG. 2, the reservoiris formed from a collection of multiple reservoirs or reservoirsections, connected by tubing 24, designed to provide a flexible orcontoured implant device shape that can form to the shape of subject'sskull, and wherein the reservoir is filled by syringe through a fillport attached to one or more of the reservoir sections and thereby fillsall reservoir sections through the connected tubing 24. In still anotherembodiment, the reservoir sections are interconnected in a manner thatprovides complete drainage of all reservoirs sections prior to refill.

[0070] In another example embodiment, the pouch 22 is formed at least inpart with a silicone or polymer.

[0071] According to yet another example embodiment of the apparatus therefill port is a sealed silicone portal that is accessed by a needlethrough the subject's skin.

[0072] Yet still another example embodiment illustrated in FIG. 3A showsa reservoir 30 deployed in the space 16 between the scalp and cranium14. More particularly in one example embodiment the reservoir 30 isretained subcutaneously between the subject's galea aponeurotica 15 andskin 13 so that the reservoir outline is imperceptible to a casualobserver. In this case or others the reservoir is anchored by suturingto the subject's galea. In another example embodiment also shown in FIG.3A and in FIG. 3B, the reservoir 30 is substantially planar, and theedges 32 of the reservoir taper from a smaller or feathered thickness 34at the edge to a greater thickness 36 away from the edge.

[0073] Referring to FIG. 4, there is illustrated in one exampleembodiment of the invention a reservoir housing 40 implanted under skin44 in the soft tissue 44 of the lower back 42 of a subject, wherein thereservoir housing 40 has a low profile or planar configuration adaptedto fit in the soft tissue of the lower back. Alternatively, the profileor configuration can be adapted to other locations on the back or otherportions of the body.

[0074] As shown in FIG. 5, one or more deployment lines 52 are connectedat or near the edge of the reservoir 50 such that when pulled deploy thereservoir 50 in a desired position. The reservoir is, in one exampleembodiment, adapted so that it conforms to the shape of the skull, forinstance with a seam between bladders running along the crest orlongitudinal center ridge of the cranium.

[0075] According to another embodiment of the apparatus of the inventionillustrated in FIG. 6, the reservoir 60 is refilled using a hypodermicneedle 62 that is inserted through the scalp or skin 12 and into arefill port 66 on the reservoir 60 adapted to receive the needle. In yetanother example embodiment, the reservoir is substantially planar, andthe port is oriented so that the needle is inserted along a line that isgenerally parallel to the plane of the reservoir. Where, in yet anotherexample embodiment, the reservoir is substantially planar, the port isoriented so that the needle is inserted along a line that is generallyperpendicular to the plane of the reservoir. As illustrated in FIG. 7, aport 72 may be located along the perimeter 74 of a reservoir 70. In FIG.8, a port 82 is illustrated positioned on the side 84 of reservoir 80.

[0076] Still another example embodiment illustrated in FIG. 9 providesfor holding one or more different therapeutic agents 92 a, 92 b and 92 cin one or more additional reservoirs 90 a, 90 b and 90 c which areimplanted under the scalp 12, and dispensing the different agents fromeach reservoir.

[0077] In a further embodiment shown in FIG. 10, wherein the reservoiris a pouch 100, and when the reservoir is full, the pouch is confined bya solid surface 102 such as the inside of an outer hermetic enclosure ora molded plastic restrainer 104.

[0078] In a still further embodiment illustrated in FIG. 11, one end ofa reservoir 110 has a fixed dimension and contains an outlet port 112and a filling port 114, with the opposing end having a non-fixeddimension activated by a push rod or piston mechanism 116 to predictablycollapse the pouch 118 while pushing the therapeutic agent out underconstant pressure. As also shown in FIG. 11, the reservoir 110 isenclosed in a solid casing 118 and a drive or stepper motor 115 retainsthe therapeutic agent and to forces the agent through the outlet port112. Thus, the pump is a diaphragm pump or piston pump that controlsdosage volume by change in volume per stroke multiplied by the number ofstrokes. In FIG. 12, the pouch 110 is shown partially collapsed bypiston mechanism 116.

[0079] Another embodiment provides that after an infusion cycle, thedrive or stepper motor 115 reverses enough to release pressure on thetherapeutic agent chamber and to maintain a neutral or slight negativepressure in relation to that of the surrounding anatomy.

[0080] In yet still another embodiment shown in FIG. 13, a screw orimpeller pump 132 is located at the fixed end of a reservoir 130 andwithdraws the agent from the reservoir 130. In one such exampleembodiment, the reservoir 130 is a pouch or bladder and agent is pumpedfrom the pouch, and the pouch collapses as it is emptied, maintainingthe appropriate pressure/volume ratio inside the pouch and therebypreventing air from entering the pouch. In an example embodiment such asshown in FIG. 13 wherein the pump is a screw or impeller, it is forexample driven by a stepper or microstepper motor 134 that is accuratelycontrolled to regulate the dosage volume by number of rotations of thescrew or impeller. In FIG. 14, the reservoir 130 is shown furtherdeflated from its form in FIG. 13, as a result of agent being withdrawn.

[0081] In one example embodiment of the apparatus shown in FIG. 15, thereservoir 150 is a square or round hollow, rigid tube 152 coiled tomaintain a flat or specifically shaped profile of minimum surface area,and the reservoir is filled through an inflow valve 154 located at ornear one end 156 of the tube, and the outflow port 157 is located at theopposite end of the tube 158 from the valve 154.

[0082] According to still another embodiment shown in FIG. 16, thetherapeutic agent is dispensed from the reservoir 160 to a location 162in the brain 164 of the subject. Such dispensing is done in one exampleembodiment based on programmed parameters. Such programmed parametersare for example telemetered transcutaneously. Further, information maybe telemetered transcutaneously to a device outside the subject's body.According to one such embodiment, the agent is dispensed using a fluidconduit 161 with a proximal end 161 a coupled to receive agent from thereservoir 160 and a distal end 161 b positioned in the brain 164 of thesubject.

[0083] In still other embodiments for example shown in FIG. 17, a firstvalve 172 regulates the inflow and a second valve 174 regulates theoutflow of agent from reservoir 170. Yet another embodiment providesthat the inflow valve 172 is a mechanical valve displaced by a refillneedle 176. In one example embodiment, the inflow valve 172 is anelectronically controlled valve that is activated by an external device178 through control unit 173 using telemetered signals 177 at the timeof filling, and/or the outflow valve is electronically controlled andtimed to the outflow cycle of the pump using control unit 173 andsignals 177 telemetered by device 178. In this arrangement, forinstance, the outflow valve 174 is a normally closed valve located atthe distal end of a catheter or tube 175 carrying the therapeutic agentto a treatment site in the subject's body, and when therapeutic agentdelivery is required, the valve 174 is electrically opened and remainsopen for a programmed period of time so that pump 179 can pump agentfrom reservoir 170 to the treatment site. According to yet one moreembodiment, conductors 171 carrying control signals to the valve 174 areembedded in the sidewall of the catheter 175. In another embodiment,valve 174 is positioned at the proximal end of conduit 175 at thedischarge port of the reservoir. According to one illustrativeembodiment, the valve 172, pump 179, control unit 173, reservoir 170 andoptionally valve 174 are mounted inside or integrated with a housing169.

[0084] In still another arrangement illustrated in FIG. 18, there isprovided a closed loop sensory mechanism 180 that determines when todeliver a dosage of therapeutic agent and how much therapeutic agentdosage is appropriate. Sensor 182 senses delivery of the therapeuticagent to treatment site 181 and provides a feedback signal toelectronics 184, which in turn controls the pump 186 to pump agent fromreservoir 188 to site 181.

[0085] Yet another example embodiment illustrated in FIG. 19 providesfor forming at least one cavity 190 in the cranium 14 of the subject,and placing at least a portion of a pump 194 in the cavity. In yetanother example embodiment, the cavity 190 is a burrhole.

[0086] Yet more example embodiments illustrated in FIG. 20 provide forpositioning control electronics or a battery 200 for the pump inside thebody 202 of the subject at a location other than the top of the head ofthe subject, such as under the skin behind the ear of 204 the subject,or alternatively (dotted lines) in the chest region 206 of the subject.

[0087] In still more embodiments as for example illustrated in FIGS. 21and 22, power 210 is transmitted by RF energy to a pump 212transcutaneously (FIG. 21) and received by a circuit 214 that convertsthe RF energy to power for the pump 212 or valve control, or as show inFIG. 22 an implanted power source 220 is retained within the subject'sbody 222, wherein the power source 220 powers a pump 224, and forexample the power source is rechargeable. Such rechargeable power sourceis a rechargeable battery or, alternatively a storage capacitor. Therechargeable power source is recharged in this embodiment, for example,by transcutaneously transmitting power to the power source. In someoperational modes, the therapeutic agent is pumped as an external powersource is placed over the site of the pump and reservoir.

[0088] As illustrated in FIG. 23, still other embodiments provide thatthe power source 230 is integral with electronic circuitry 232 used tocontrol a pump 234.

[0089] The apparatus of the invention further provides in one examplearrangement as illustrated in FIG. 24, for forming at least one cavity240 in the cranium of the subject 242, and placing at least a portion ofthe power source 244 in the cavity. As shown in FIG. 24, the powersource is proximate or integral a reservoir housing 245. Alternatively,in another embodiment, the electronics are also mounted in the burr holewith the battery. The power source is a rectifier or battery.

[0090] Referring to FIG. 25, there is illustrated in three dimensionalschematic form an example embodiment showing a pair of reservoirs 250 aand 250 b positioned generally on the top of a subject's cranium, oneither side of the crown, with each reservoir including a refill port252 a and 252 b connected to each respective reservoir with a fluidconduit. The refill ports 252 a and 252 b are preferably positionedbehind each ear such that a refill syringe can be inserted through theskin into the port without the requirement of shaving hair from thesubject's scalp to obtain a clean entry path. The reservoirs areconnected with a fluid conduit 254. A further fluid conduit 256 carriestherapeutic agent from one of the reservoirs to a burrhole access intothe subject's brain, and a catheter carries the therapeutic agent fromthe access point into the brain.

[0091] In yet more example embodiments of the apparatus, more than onecavities or burrholes are formed in a subject's cranium, and at least aportion of a pump is retained in one cavity and at least a portion of apower source for the pump in the other cavity.

[0092] As illustrated in FIG. 26, an external device 260 is provided onone example embodiment to telemeter signals 262 into and out ofimplanted electronic circuitry 264. In such an example embodiment, theexternal device 260 reprograms the electronic circuitry 264 asnecessary, and collects and displays data 265 as transmitted from theimplantable device. Further, the external electronic device 260 in someembodiments signals the electronic circuitry 264 to cause an extra doseof therapeutic agent to be delivered upon demand by an operator. In someexample configurations, the bidirectional transmitting provides signalsto activate the circuitry within the implant device and relay statusinformation from the circuitry 264 to outside the subject's body. Suchsignals include in some example cases starting energy and signaltransmission either automatically by proximity of the external device tothe implanted device or by a control activated by an operator.

[0093] According to one example embodiment of the invention, thedimensions are as follows, for implant under the scalp, are as follows:

[0094] Housing volume: approximately less than or equal to 50 cc.

[0095] Thickness (side profile) of housing: approximately 3-5 mm.

[0096] Thickness (side profile) of housing including for exampleelectronics/battery burrhole section(s): approximately 12-14 mm.

[0097] Maximum housing dimension in length or width: approximately 145mm.

[0098] According to such example embodiment, the housing may enclose orhouse the reservoir and/or pump and/or other components such as theelectonics and power source.

[0099] According to one illustrative embodiment, these parameters arethe totals for both housings if more than one housing is used.

[0100] According to another example embodiment of the spinalreservoir/pumping invention, for implant in the back for use with spinaltreatments, are as follows:

[0101] Housing volume: approximately less than or equal to 50 cc.

[0102] Thickness (side profile) of housing: approximately 5-10 mm.

[0103] Maximum housing dimension in length or width: approximately 110mm. (including reservoir and/or pump and/or other components

[0104] According to one illustrative embodiment, these parameters arethe totals for both housings if more than one housing is used.

[0105] Although specific embodiments have been illustrated and describedherein, it will be appreciated by those of ordinary skill in the artthat any arrangement which is calculated to achieve the same purpose maybe substituted for the specific embodiments shown. This application isintended to cover any adaptations or variations of the invention. It ismanifestly intended that this invention be limited only by the followingclaims and equivalents thereof.

We claim:
 1. A method comprising retaining a reservoir for a therapeuticagent between the scalp and cranium of a subject.
 2. A method accordingto claim 1 wherein the reservoir is hermetically sealed with a metal. 3.A method according to claim 2 wherein the metal is a foil.
 4. A methodaccording to claim 1 further wherein the reservoir comprises one or morebladders adapted to occupy a substantially planar space between thescalp and cranium.
 5. A method according to claim 4 further whereinthere is more than one bladder and the bladders are connected with atleast one fluid conduit allowing therapeutic agent to flow from onebladder to the other.
 6. A method according to claim 1 further includingrefilling the reservoir using a hypodermic needle that is insertedthrough the scalp and into a refill port on the reservoir adapted toreceive the needle.
 7. A method according to claim 6 wherein thereservoir is substantially planar, and the port is oriented so that theneedle is inserted along a line that is generally parallel to the planeof the reservoir.
 8. A method according to claim 6 wherein the reservoiris substantially planar, and the port is oriented so that the needle isinserted along a line that is generally perpendicular to the plane ofthe reservoir.
 9. A method according to claim 1 wherein the reservoir issubstantially planar, and the edges of the housing of the reservoirtaper from a smaller thickness at the edge to a greater thickness awayfrom the edge.
 10. A method according to claim 1 further includingdeploying the reservoir in the space between the scalp and cranium usingone or more deployment lines connected at or near the edge of thereservoir that when pulled deploy the reservoir in a desired position.11. A method according to claim 1 including one or more additionalreservoirs holding one or more different therapeutic agents.
 12. Amethod according to claim 1 including retaining the reservoirsubcutaneously between the subject's scalp and cranium so that thereservoir outline is imperceptible to a casual observer.
 13. A methodaccording to claim 1 further including anchoring the reservoir bysuturing to the subject's galia.
 14. A method according to claim 1further wherein the reservoir is a pouch that is held dimensionallyfixed on all axes except one.
 15. A method according to claim 14 furtherwherein the reservoir is formed at least in part with a silicone orpolymer.
 16. A method according to claim 1 wherein the reservoir is apouch, and when the reservoir is full, the pouch is confined by a solidsurface such as the inside of an outer hermetic enclosure or a moldedplastic restrainer.
 17. A method according to claim 2 further whereinone end of the reservoir has a fixed dimension and contains an outletport and a filling port, with the opposing end having a non-fixeddimension and is activated by a push rod or piston mechanism topredictably collapse the pouch while pushing the therapeutic agent outunder constant pressure.
 18. A method according to claim 17 wherein ascrew or impeller pump is located at the fixed end of the reservoir andwithdraws the agent from the reservoir.
 19. A method according to claim2 wherein the reservoir is a pouch and the agent is pumped from thepouch, and the pouch collapses as it is emptied, maintaining theappropriate pressure/volume ratio inside the pouch and therebypreventing air from entering the pouch.
 20. A method according to claim1 wherein the reservoir is a solid cylinder with the outlet port orvalve mechanism located on one end of the cylinder, and the opposing endis fitted with a push rod/sealing piston to retain the therapeutic agentand to force the therapeutic agent through the outlet port.
 21. A methodaccording to claim 20 further wherein after an infusion cycle, the driveor stepper motor reverses enough to release pressure on the therapeuticagent chamber and to maintain a neutral or slight negative pressure inrelation to that of the surrounding anatomy.
 22. A method according toclaim 2 wherein the reservoir is a square or round hollow, rigid tubecoiled to maintain a flat or specifically shaped profile of minimumsurface area, and the reservoir is filled through an inflow valvelocated at or near one end of the tube, and the outflow port is locatedat the opposite end of the tube from the filling port.
 23. A methodaccording to claim 2 further wherein the reservoir is a collection ofmultiple reservoirs, connected by tubing, designed to provide a flexibleor contoured implant device shape that can form to the shape ofsubject's skull, and wherein the reservoir is filled by syringe througha fill port attached to one of the reservoir sections and thereby fillsall reservoir sections through the connected tubing.
 24. A methodaccording to claim 23 further including a pump located in a manner thatprovide complete drainage of all reservoir sections during a therapycycle.
 25. A method according to claim 2 wherein refill of the reservoiris accomplished through a sealed silicone portal that is accessed by aneedle through the skin.
 26. A method according to claim 1 wherein thereservoir is of a shape substantially that of the top of a human head.27. A method according to claim 1 further including dispensing thetherapeutic agent from the reservoir to a location in the brain of thesubject.
 28. A method according to claim 1 further including dispensingtherapeutic agent from the reservoir to a treatment site in the spine ofthe subject.
 29. A method according to claim 27 further includingdispensing the therapeutic agent based on programmed parameters.
 30. Amethod according to claim 27 further including dispensing thetherapeutic agent based on signals telemetered transcutaneously.
 31. Amethod according to claim 27 including telemetering dispensinginformation transcutaneously to a device outside the subject's body. 32.A method according to claim 27 including dispensing the agent with afluid conduit with a proximal end coupled to receive agent from thereservoir and a distal end positioned in the brain of the subject.
 33. Amethod according to claim 28 including dispensing the agent with a fluidconduit with a proximal end coupled to receive agent from the reservoirand a distal end positioned in or proximate the spine of the subject.34. A method according to claim 1 further including dispensing avariable dosage of therapeutic agent from the reservoir to a treatmentsite.
 35. A method according to claim 1 further including dispensing atimed dosage of therapeutic agent from the reservoir.
 36. A methodaccording to claim 27 wherein the agent is dispensed by pumping it tothe location in the subject's body with a pump, the pump is a diaphragmpump or piston pump that controls dosage volume by change in volume perstroke X number of strokes, and further including controlling the flowof agent using a first valve to regulate the inflow and a second valveto regulate the outflow wherein the inflow valve is a mechanical valvedisplaced by the refill needle.
 37. A method according to claim 27wherein the agent is dispensed by pumping it to the location in thesubject's body with a pump, the pump is a diaphragm pump or piston pumpthat controls dosage volume by change in volume per stroke X number ofstrokes, and further including controlling the flow of agent using afirst valve to regulate the inflow and a second valve to regulate theoutflow wherein the inflow valve is an electronically controlled valvethat is activated by an external device at the time of filling.
 38. Amethod according to claim 27 wherein the agent is dispensed by pumpingit to the location in the subject's body with a pump, the pump is adiaphragm pump or piston pump that controls dosage volume by change involume per stroke X number of strokes, and further including controllingthe flow of agent using a first valve to regulate the inflow and asecond valve to regulate the outflow wherein the outflow valve iselectronically controlled and timed to the outflow cycle of the pump.39. A method according to claim 27 wherein the agent is dispensed bypumping it to the location in the subject's body with a pump, the pumpis a diaphragm pump or piston pump that controls dosage volume by changein volume per stroke X number of strokes, and further includingcontrolling the flow of agent using a first valve to regulate the inflowand a second valve to regulate the outflow wherein the outflow valve isa normally closed valve located at the distal end of a catheter carryingthe therapeutic agent to the location in the subject's body, and whentherapeutic agent delivery is required, the valve is electrically openedand remains open for a programmed period of time.
 40. A method accordingto claim 39 further wherein conductors for the valve are embedded in thesidewall of the catheter.
 41. A method according to claim 27 wherein theagent is dispensed by pumping it to the location in the subject's bodywith a pump and further including retaining an implanted power sourcewithin the subject's body wherein the power source powers the pump. 42.A method according to claim 41 wherein power source is rechargeable. 43.A method according to claim 42 wherein power source is rechargeablebattery or storage capacitor.
 44. A method according to claim 43 whereinthe power source is integral with electronic circuitry used to controlthe pump.
 45. A method according to 42 including transcutaneouslytransmitting power to the power source to recharge the power source. 46.A method according to claim 42 further including pumping the therapeuticagent as an external power source is placed over the site of the pump.47. A method according to claim 42 further including forming at leastone cavity in the cranium of the subject, and placing at least a portionof the power source in the cavity.
 48. A method according to claim 27wherein the agent is dispensed by pumping it to the location in thesubject's body with a pump and further including positioning the powersource inside the body of the subject at a location other than the topof the head of the subject.
 49. A method according to claim 27 whereinthe agent is dispensed by pumping it to the location in the subject'sbody with a pump and further including positioning the power sourceunder the skin behind the ear of the subject.
 50. A method according toclaim 27 wherein the agent is dispensed by pumping it to the location inthe subject's body with a pump and further including positioning thepower source in the chest region of the subject.
 51. A method accordingto claim 1 further including one or more electronic components adaptedto control the dispensing of therapeutic agent from the reservoir to thesubject's body and containing the electronic components or pump in ahermetically sealed container suitable for long term human implant. 52.A method according to claim 51 wherein the container is constructed ofone or more materials from the following group: titanium and stainlesssteel.
 53. A method according to claim 1 further including forming atleast two cavities in the cranium of the subject, and placing at least aportion of a pump in one cavity and at least a portion of a power sourcefor the pump in the other cavity.
 54. A method according to claim 27further including electronic circuitry operating the pump based onprogrammed parameters and a device external to the subject's body totelemeter signals into and out of the electronic circuitry.
 55. A methodaccording to 54 wherein the external device reprograms the electroniccircuitry as necessary, and collects and displays data as transmittedfrom the implantable device.
 56. A method according to claim 54 whereinthe external device may signal the electronic circuitry to cause anextra dose of therapeutic agent to be delivered upon demand by anoperator.
 57. A method according to claim 27 further includingelectronic circuitry operating the pump based on programmed parametersand bidirectionally transmitting signals to activate the circuitrywithin the implant device and relay status information from thecircuitry to outside the subject's body.
 58. A method according to claim57 including starting energy and signal transmission eitherautomatically by proximity of the external device to the implanteddevice or by a control activated by an operator.
 59. A method accordingto claim 27 further including electronic circuitry operating the pumpbased on programmed parameters wherein the components are enclosed in afluid-tight enclosure and all electrical components and connections arehermetically sealed against potential moisture related failures.
 60. Amethod according to claim 27 further including a pump and power source,and further wherein the pump and power source are housed integral to thepump and reservoir.
 61. A method according to claim 27 further includinga pump and power source, and further wherein the pump or power sourceare located remotely from the reservoir.
 62. A method according to claim61 further wherein the pump or power source are implanted in thesubject's body.
 63. A method according to claim 61 wherein single ormultiple conductors carry power from the power source to the pump.
 64. Amethod according to claim 63 further including encasing the conductorsin a biocompatible flexible material.
 65. A method according to claim 64further wherein the biocompatible material is selected from the groupof: silicone or polyurethane and wherein the conductors are permanentlyattached to the pump and electronic components for controlling the pumpin a manner that allows them to be disconnected.